The hippocampus is part of the brain's limbic system which controls emotional behavior, motivational drive, and other physiological functions. The limbic system includes the limbic cortex, hippocampus, amygdala, hypothalamus, and anterior thalamus. The hippocampus plays an important role in learning processes and certain types of memory. Stimulation of the hippocampus can cause behavioral responses including rage, passivity, and excess sex drive. Weak electrical stimulation can cause hippocampal seizures. Individuals who lose hippocampal function retain memory for events that occurred prior to the loss and only have immediate memory, lasting less than a few minutes, for all events after the loss (anterograde amnesia). Thus, the hippocampus is thought to interpret the importance of incoming sensory information and to determine what input is worth remembering. The hippocampus then transmits signals that make the mind rehearse the information over and over again until permanent storage takes place.
Numerous studies of the effects of ablation of the hippocampus of rodent, primate, and other non-human species have been conducted. Memory disorders and spatial performance are associated with hippocampal function. Morphological changes in the hippocampus, including cell loss, is associated with epilepsy, schizophrenia, Alzheimer's disease, and certain amnesiac syndromes. (Jack (1994) Epilepsia 35:S21-S29). Research data from animals show glucocorticoids secreted during stress can damage the hippocampus and impair the ability of hippocampal neurons to survive neurological insults. (Sapolsky (1993) Behav. Brain Res. 57:175-82). Sustained glucocorticoid exposure might damage the hippocampus in humans as well; hippocampal atrophy has been reported in patients with Cushing's syndrome as a result of the hypersecretion of glucocorticoids.
Phylogenetic relationships among organisms have been demonstrated many times, and studies from a diversity of prokaryotic and eukaryotic organisms suggest a more or less gradual evolution of biochemical and physiological mechanisms and metabolic pathways. Despite different evolutionary pressures, proteins that regulate the cell cycle in yeast, nematode, fly, rat, and man have common chemical or structural features and modulate the same general cellular activity. Comparisons of human gene sequences with those from other organisms where the structure and/or function may be known allow researchers to draw analogies and to develop model systems for testing hypotheses. These model systems are of great importance in developing and testing diagnostic and therapeutic agents for human conditions, diseases and disorders.
Identification of genes that participate in hippocampal development provide new potential diagnostic and therapeutic targets. The present invention satisfies a need in the art by providing new compositions that are useful for diagnosis, prognosis, treatment, prevention, and evaluation of therapies for diseases associated with hippocampus such as Alzheimer's disease, Huntington's disease, schizophrenia, epilepsy, and their complications.